Genetic Variant SLC22A6:c.-127G>A (chr11-62984817-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153276.3(SLC22A6):c.-127G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,086,636 control chromosomes in the GnomAD database, including 8,846 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 3094 hom., cov: 31)

Exomes 𝑓: 0.096 ( 5752 hom. )

Consequence

SLC22A6
NM_153276.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.284

Publications

28 publications found

Variant links:

Genes affected

SLC22A6 (HGNC:10970): (solute carrier family 22 member 6) The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SLC22A6 links:

ENSG00000301851 (HGNC:):

ENSG00000301851 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153276.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC22A6	NM_153276.3	MANE Select	c.-127G>A	5_prime_UTR	Exon 1 of 10	NP_695008.1
SLC22A6	NM_004790.5		c.-127G>A	5_prime_UTR	Exon 1 of 10	NP_004781.2
SLC22A6	NM_153278.3		c.-127G>A	5_prime_UTR	Exon 1 of 10	NP_695010.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC22A6	ENST00000360421.9	TSL:1 MANE Select	c.-127G>A	5_prime_UTR	Exon 1 of 10	ENSP00000353597.4
SLC22A6	ENST00000377871.7	TSL:1	c.-127G>A	5_prime_UTR	Exon 1 of 10	ENSP00000367102.3
SLC22A6	ENST00000540654.5	TSL:5	n.-127G>A	non_coding_transcript_exon	Exon 1 of 10	ENSP00000445946.1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25377

AN:

151982

Hom.:

3067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0852

Gnomad OTH

AF:

0.150

GnomAD4 exome

AF:

0.0960

AC:

89723

AN:

934538

Hom.:

5752

Cov.:

AF XY:

0.0974

AC XY:

45415

AN XY:

466036

show subpopulations

African (AFR)

AF:

0.331

AC:

7005

AN:

21152

American (AMR)

AF:

0.116

AC:

2490

AN:

21394

Ashkenazi Jewish (ASJ)

AF:

0.0853

AC:

1440

AN:

16878

East Asian (EAS)

AF:

0.230

AC:

7679

AN:

33356

South Asian (SAS)

AF:

0.157

AC:

8851

AN:

56254

European-Finnish (FIN)

AF:

0.100

AC:

3120

AN:

31084

Middle Eastern (MID)

AF:

0.164

AC:

489

AN:

2978

European-Non Finnish (NFE)

AF:

0.0762

AC:

54035

AN:

709540

Other (OTH)

AF:

0.110

AC:

4614

AN:

41902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3977

7955

11932

15910

19887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1830

3660

5490

7320

9150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25452

AN:

152098

Hom.:

3094

Cov.:

AF XY:

0.167

AC XY:

12429

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.335

AC:

13879

AN:

41470

American (AMR)

AF:

0.117

AC:

1795

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0836

AC:

290

AN:

3470

East Asian (EAS)

AF:

0.244

AC:

1256

AN:

5146

South Asian (SAS)

AF:

0.174

AC:

840

AN:

4822

European-Finnish (FIN)

AF:

0.107

AC:

1138

AN:

10600

Middle Eastern (MID)

AF:

0.140

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0852

AC:

5790

AN:

67968

Other (OTH)

AF:

0.155

AC:

328

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1002

2004

3006

4008

5010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.108

Hom.:

1848

Bravo

AF:

0.177

Asia WGS

AF:

0.209

AC:

728

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.28

PromoterAI

0.0096

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over